Caffeic acid selectively eliminates teratogenic human-induced pluripotent stem cells via apoptotic cell death.
Phytomedicine
; 102: 154144, 2022 Jul 20.
Article
in En
| MEDLINE
| ID: mdl-35537368
BACKGROUND: Induced pluripotent stem cells (iPSCs) generated from reprogrammed adult somatic cells are considered as a promising cell source in cell-based regenerative medicine. To avoid teratoma formation, which is a safety issue in iPSC-based cell therapy, it is important to selectively remove undifferentiated iPSCs that remain in the differentiated cell product before in vivo transplantation. Caffeic acid (CAA, 3,4-dihydroxy-cinnamic acid) is a phenolic compound synthesized from various vegetables, fruits, and herbs; it has shown various pharmacological activities against inflammation, cancer, infection, diabetes, and neurodegenerative diseases. However, the beneficial effects of CAA in iPSC-based cell therapy, such as the selective elimination of iPSCs and anti-teratoma effects, have not yet been explored. RESULTS: Here, we found that CAA induced apoptotic cell death in iPSCs; this process did not occur in iPSC-derived mesenchymal progenitor cells (MPCs) or human dermal fibroblast (hDFs). Under co-culture conditions with MPCs and hDFs, CAA treatment selectively removed iPSCs. In addition, CAA treatment in mixed cell culture with iPSCs and MPCs prior to grafting markedly suppressed iPSC-derived teratoma formation. Finally, CAA did not induce DNA damage in MPCs or hDFs. CONCLUSION: Taken together, these results suggest that CAA is effective in preparing safe iPSC-based therapeutic cells without the risk of teratoma formation and DNA damage in normal cells and iPSC-derived differentiated cells.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Teratoma
/
Induced Pluripotent Stem Cells
Limits:
Adult
/
Humans
Language:
En
Journal:
Phytomedicine
Journal subject:
TERAPIAS COMPLEMENTARES
Year:
2022
Document type:
Article
Country of publication:
Germany